Renal cell carcinoma biomarkers

Abstract

Disclosed herein is a method of identifying a tumor biomarker. In one example, a tumor biomarker is identified by obtaining a peripheral biological fluid sample from a subject with a tumor as well as a tumor sample and an adjacent non-tumor sample from such subject. A protein expression profile is detected in the peripheral biological fluid sample, tumor sample and adjacent non-tumor sample. The protein expression profiles of the peripheral biological fluid sample, tumor sample and adjacent non-tumor sample are then compared, wherein an increase in expression of a specific protein in the tumor sample and peripheral biological fluid sample but not in the adjacent non-tumor sample indicates that the specific protein is a biomarker of the tumor. Also disclosed herein is a gene profiling signature that can be used to diagnosis a subject with renal cell carcinoma (RCC) or to identify agents with therapeutic potential to treat RCC. Thus, methods of diagnosing a subject with RCC are disclosed. Methods are also provided for identifying agents that alter an activity of a RCC biomarker.

We claim: 
     
       1. A method of diagnosing renal cancer, comprising:
 obtaining a biological sample from a subject with renal cancer or suspected of having renal cancer; 
 contacting a sample obtained from the subject with renal cancer or suspected of having renal cancer with at least two antibodies capable of detecting at least two of cadherin-5 precursor, cadherin-11 precursor, pyruvate kinase isozymes M1/M2, and probable ATP-dependent RNA helicase (DDX23); 
 measuring protein expression of at least two of cadherin-5 precursor, cadherin-11 precursor, pyruvate kinase isozymes M1/M2, and probable ATP-dependent RNA helicase (DDX23) in a biological sample obtained from a subject with renal cancer or suspected of having renal cancer by performing Western Blot analysis or an enzyme-linked immunosorbent assay (ELISA) that detects at least two of cadherin-5 precursor, cadherin-11 precursor, pyruvate kinase isozymes M1/M2, and probable ATP-dependent RNA helicase (DDX23); and 
 determining the presence of renal cancer in the subject by comparing protein expression level of at least two or more of proteins cadherin-5 precursor, cadherin-11 precursor, pyruvate kinase isozymes M1/M2, and probable ATP-dependent RNA helicase (DDX23) in the sample obtained from the subject with renal cancer or suspected of having renal cancer with the protein expression level of the at least two or more proteins expressed in a non-tumor sample wherein an at least 2-fold increase in protein expression level of at least two or more of these proteins relative to protein expression level in the non-tumor sample indicates that the subject has renal cancer. 
 
     
     
       2. The method of  claim 1 , wherein the biological sample comprises renal cancer. 
     
     
       3. The method of  claim 1 , wherein the biological sample comprises serum or plasma. 
     
     
       4. The method of  claim 1 , wherein measuring protein expression is by Western Blot analysis. 
     
     
       5. The method of  claim 3 , wherein measuring protein expression is by enzyme-linked immunosorbent assay (ELISA). 
     
     
       6. The method of  claim 5 , wherein the biological sample comprising serum or plasma is obtained prior to surgery. 
     
     
       7. The method of  claim 1 , wherein measuring protein expression of at least two of cadherin-5 precursor, cadherin-11 precursor, pyruvate kinase isozymes M1/M2, and probable ATP-dependent RNA helicase (DDX23) in a biological sample obtained from a subject with renal cancer or suspected of having renal cancer comprises measuring cadherin-5 precursor, cadherin-11 precursor, and probable ATP-dependent RNA helicase (DDX23). 
     
     
       8. The method of  claim 1 , wherein the antibodies are humanized antibodies.